Altitude, Exercise, and Skeletal Muscle Angio-Adaptive Responses to Hypoxia: A Complex Story

Abstract

Hypoxia, defined as a reduced oxygen availability, can be observed in many tissues in response to various physiological and pathological conditions. As a hallmark of the altitude environment, ambient hypoxia results from a drop in the oxygen pressure in the atmosphere with elevation. A hypoxic stress can also occur at the cellular level when the oxygen supply through the local microcirculation cannot match the cells’ metabolic needs. This has been suggested in contracting skeletal myofibers during physical exercise. Regardless of its origin, ambient or exercise-induced, muscle hypoxia triggers complex angio-adaptive responses in the skeletal muscle tissue. These can result in the expression of a plethora of angio-adaptive molecules, ultimately leading to the growth, stabilization, or regression of muscle capillaries. This remarkable plasticity of the capillary network is referred to as angio-adaptation. It can alter the capillary-to-myofiber interface, which represent an important determinant of skeletal muscle function. These angio-adaptive molecules can also be released in the circulation as myokines to act on distant tissues. This review addresses the respective and combined potency of ambient hypoxia and exercise to generate a cellular hypoxic stress in skeletal muscle. The major skeletal muscle angio-adaptive responses to hypoxia so far described in this context will be discussed, including existing controversies in the field. Finally, this review will highlight the molecular complexity of the skeletal muscle angio-adaptive response to hypoxia and identify current gaps of knowledges in this field of exercise and environmental physiology.

Training at moderate altitude improves submaximal but not maximal performance-related parameters in elite rowers

“…However, our results showed an increase in hematological parameters without a concomitant increase in V_O 2max , showing a decoupling between the increase in oxygen transport capacity and its consumption. A probable explanation is that hypoxia could induce cellular signaling (e.g., HIF-1; VEGF), responsible for neovascularization by activating angiogenic mechanisms that mediate skeletal muscle adaptations (Lemieux and Birot, 2021). Besides, training in hypoxia could increase transcript levels of regulators of mitochondrial biogenesis as well as mitochondrial metabolism (Zoll et al, 2006), which could substantially impact training adaptation and exercise performance as physiological thresholds and efficiency/economy.…”

Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils the Characteristics of the Immune Microenvironment and Prognosis Signature in Prostate Cancer

“…To date, to the best of our knowledge, there is no direct evidence that muscle tissue development is associated with cancer progression. Hypoxia occurring within the muscle during exercise could stimulate angiogenesis [30][31][32]. Moreover, hypoxia is common in many cancers [33].…”

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“…We found that in the Responders, the exercise-induced increase in HIF-1α was reduced after SP supplementation. HIF-1α is a well-established hallmark of hypoxia signaling and it plays an important role in both the acute responses and the long-term cellular adaptations to oxygen deficiency [72,73]. It has been demonstrated that hypoxia and exercise stimulate HIF-1α activation in response to a reduction in intracellular oxygen tension in skeletal muscles [74][75][76].…”